Amyloid beta (Aβ), tau, and neurodegeneration jointly with the Alzheimer\'s disease (AD) risk factors affect the severity of clinical symptoms and disease progression.
Within 248 Aβ-positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake, and regional magnetic resonance imaging-based atrophy) and risk-factors (age, sex, education, apolipoprotein E [APOE], and white-matter lesions) on cross-sectional cognitive impairment and longitudinal cognitive decline.
Sixteen percent of variance in cross-sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ-tau-atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively.
These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.

Background: Acupuncture may be a promising complementary therapy for vascular cognitive impairment (VCI) and has been extensively applied in China. However, its potential effects remain uncertain, and the clinical findings are inconsistent. This review aimed to systematically appraise the overall effectiveness and safety of acupuncture in treating VCI. Methods: To investigate the effects of acupuncture on VCI from inception to February 28, 2021 using randomized clinical trials (RCTs), seven electro-databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang] were searched. Two independent investigators identified the eligible RCTs and extracted data into predesigned forms. The risk of bias (ROB) within each individual trial was evaluated using the Cochrane Collaboration\'s tool. Meta-analyses were conducted for calculating comparative effects in the RevMan software (version 5.3). The strength of attained evidence was rated using the online GRADEpro approach. Results: A total of 48 RCTs involving 3,778 patients with VCI were included. The pooled data demonstrated that acupuncture was more beneficial for a global cognitive function [mean difference (MD) 1.86, 95% CI 1.19-2.54, p < 0.01] and activities of daily living (MD -3.08, 95% CI -4.81 to -1.35, p < 0.01) compared with western medicine (WM). The favorable results were also observed when acupuncture was combined with WM (MD 2.37, 95% CI 1.6-3.14, p < 0.01) or usual care (UC, MD 4.4, 95% CI 1.61-7.19, p = 0.002) in comparison with the corresponding control conditions. Meanwhile, the subgroup analysis did not indicate a statistical effect difference between manual acupuncture (MA) and electroacupuncture (EA) (inter-group I 2 < 50% and p > 0.1) when comparing acupuncture with WM. There were no significant differences in the occurrence of adverse events (AEs) between the acupuncture group and the control group (p > 0.05). Owing to the poor methodological quality and considerable heterogeneity among studies, the certainty of the evidence was low or very low. Conclusions: This review suggests that acupuncture as a monotherapy or an adjuvant therapy may play a positive role in improving the cognition and daily performance of VCI patients associated with few side effects. The difference in styles may not significantly influence its effectiveness. More rigorously designed and preregistered RCTs are highly desirable to verify the therapeutic benefits and determine an optimal acupuncture paradigm. The methodological and reporting quality of future researches should be enhanced by adhering to authoritative standardized statements. Systematic Review Registration: [PROSPERO], identifier [No. CRD42017071820].

Mild cognitive impairment (MCI) is a condition that may be prodromal to the development of dementia. There remain, as yet, no approved pharmaceutical interventions for MCI. Chinese herbal medicines (CHMs) have a long history of use for cognitive impairments and some plant ingredients have shown neuroprotective actions in experimental studies. This review assesses the current clinical evidence from controlled clinical trials for the effects of CHMs on cognitive outcomes as measured by Mini-mental state examination (MMSE) or Alzheimer\'s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Fifty one studies (4026 participants) were included. These compared CHM with placebo, supportive care, pharmaceutical treatment or combined CHM with a pharmaceutical in an integrative setting. For the eight randomised controlled trials (RCTs) of comparisons with placebo, MMSE was significantly higher in the CHM groups (MD 1.56 [0.78, 2.34] I2  = 85%, n = 503), similarly for eight RCTs of comparisons with supportive care (MD 1.77 [1.33, 2.21] I2  = 0%, n = 555). Benefits were also evident in comparisons with some pharmaceuticals and with integrative treatment. The small size of most studies and methodological weaknesses mean that these results should be interpreted with caution. Further studies employing rigorous methods are required to investigate the potential benefits of these CHMs for MCI. Copyright © 2016 John Wiley & Sons, Ltd.

BACKGROUND: Although the Clinical Dementia Rating Scale-Sum of Boxes score (CDR-SB) is a widely accepted and commonly used global scale, validated clinical endpoints of cognitive changes are unavailable in the predementia stages of Alzheimer\'s disease (AD), and a new clinical assessment with reliability and sensitivity is needed in the mild cognitive impairment (MCI) population.
METHODS: Using Alzheimer\'s Disease Neuroimaging Initiative (ADNI)-1/GO data, signal-to-noise ratios (SNRs) were calculated to quantify the sensitivity of a measure for detecting disease progression and hypothetical treatment effects. All possible combinations of selected sensitive measures were assessed for developing composite scores. The analyses were performed in the MCI population and subpopulations enriched by apolipoprotein E4 (APOE ε4), hippocampal volume, and cerebrospinal fluid β-amyloid.
RESULTS: The best composite score was \"Word Recall + Delayed Word Recall + Orientation + CDR-SB + FAQ\", more sensitive than 13-item Alzheimer\'s Disease Assessment Scale-cognitive subscale or CDR-SB.
CONCLUSIONS: The proposed composite score derived from the existing clinical endpoints demonstrated higher sensitivity in the MCI population and is easy to implement and standardize across studies.